Transcriptional immunoresponse of tissue-specific macrophages in swine after infection with African swine fever virus

Andrzej Kowalczyk 1 , Edyta Kozak 1 , Magdalena Łyjak 1 , Zygmunt Pejsak 1 , and Krzysztof Niemczuk 1
  • 1 Department of Swine Diseases, National Veterinary Research Institute, 24-100 Pulawy, Poland


Macrophages and cytokines are important in the control of inflammation and regulation of the immune response. However, they can also contribute to immunopathology in the host after viral infection and the regulatory network can be subverted by infectious agents, including viruses, some of which produce cytokine analogues or have mechanisms that inhibit cytokine function. African swine fever virus (ASFV) encodes a number of proteins which modulate cytokine and chemokine induction, host transcription factor activation, stress responses, and apoptosis. The aim of this review is to elucidate the mechanisms of immune responses to ASFV in different subpopulations of porcine macrophages. A transcriptional immune response in different resident tissue macrophages following ASFV infection was presented in many publications. ASFV-susceptible porcine macrophages can be of several origins, such as peripheral blood, lungs, bone marrow, etc. blood monocytes, blood macrophages, and lung macrophages have demonstrated a modulation of phenotype. Monocyte-derived macrophages could express surface markers not found on their monocyte precursors. Moreover, they can undergo further differentiation after infection and during inflammation. When viruses infect such cells, immunological activity can be seriously impaired or modified.

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  • 1. Afonso C.L., Piccone M.E., Zaffuto K.M., Neilan J., Kutish G.F., Lu Z., Balinsky C.A., Gigg T.R., Bean T.J., Zsak L., Rock D.L.: African swine fever virus multigene family 360 and 530 genes affect host interferon response. J Virol 2004, 78, 1858-1864.

  • 2. Alcami A., Lira S.A.: Modulation of chemokine activity by viruses. Curr Opin Immunol 2010, 22, 482-487.

  • 3. Alonso C., Galindo I., Cuesta-Geijo M.A., Cabezas M., Hernaez B., Muñoz-Moreno R.: African swine fever virus-cell interactions: from virus entry to cell survival. Virus Res 2013, 173, 42-57.

  • 4. Basta S., Knoetig S.M., Spagnuolo-Weaver M., Allan G., McCullough K.C.: Modulation of monocytic cell activity and virus susceptibility during differentiation into macrophages. J Immunol 1999, 162, 3961-3969.

  • 5. Blome S., Gabriel C., Beer M.: Pathogenesis of African swine fever in domestic pigs and European wild boar. Virus Res 2013, 173, 122-130.

  • 6. Chamorro S., Revilla C., Alvarez B., Alonso F., Ezquerra A., Domínguez J.: Phenotypic and functional heterogeneity of porcine blood monocytes and its relation with maturation. Immunology 2005, 114, 63-71.

  • 7. Chitko-McKown C.G., Chapes S.K., Miller L.C., Riggs P.K., Ortega M.T., Green B.T., McKown R.D.: Development and characterization of two porcine monocyte-derived macrophage cell lines. Results in Immunology, Vol. 3, 2013, 26-32.

  • 8. de Oliveira V.L., Almeida S.C.P., Soares H.R., Crespo A., Marshall-Clarke S., Parkhouse R.M.E. A novel TLR3 inhibitor encoded by African swine fever virus (ASFV). Arch Virol 2011, 156, 597-609.

  • 9. Falvo J.V., Uglialoro A.M., Brinkman B.M., Merika M., Parekh B.S., Tsai E.Y., King H.C., Morielli A.D., Peralta E.G., Maniatis T., Thanos D., Goldfeld A.E.: Stimulus-specific assembly of enhancer complexes on the tumor necrosis factor alpha gene promoter. Mol Cell Biol 2000, 20, 2239-2247.

  • 10. Fishbourne E., Abrams C.C., Takamatsu H.H., Dixon L.K.: Modulation of chemokine and chemokine receptor expression following infection of porcine macrophages with African swine fever virus. Vet Microbiol 2013, 162, 937-943.

  • 11. Galindo I., Cuesta-Geijo M.A., Hlavova K., Muñoz-Moreno R., Barrado-Gil L., Dominguez J., Alonso C.: African swine fever virus infects macrophages, the natural host cells, via clathrin- and cholesterol-dependent endocytosis. Virus Res 2015, 200, 45-55.

  • 12. Ganguly D., Paul K., Bagchi J., Rakshit S., Mandal L., Bandyopadhyay G., Bandyopadhyay S.: Granulocyte-macrophage colony-stimulating factor drives monocytes to CD14low CD83+ DCSIGN- interleukin-10-producing myeloid cells with differential effects on T-cell subsets. Immunology 2007, 121, 499-507.

  • 13. Gil S., Sepúlveda N., Albina E., Leitão A., Martins C.: The lowvirulent African swine fever virus (ASFV/NH/P68) induces enhanced expression and production of relevant regulatory cytokines (IFNalpha, TNFalpha and IL12p40) on porcine macrophages in comparison to the highly virulent ASFV/L60. Arch Virol 2008, 153, 1845-1854.

  • 14. Gómez-Villamandos J.C., Bautista M.J., Sánchez-Cordón P.J., Carrasco L.: Pathology of African swine fever: the role of monocyte-macrophage. Virus Res 2013, 173, 140-149.

  • 15. Gómez-Villamandos J.C., Hervás J., Méndez A., Carrasco L., Villeda C.J., Wilkinson P.J., Sierra M.A.: Ultrastructural study of the renal tubular system in acute experimental African swine fever: virus replication in glomerular mesangial cells and in the collecting ducts. Arch Virol 1995, 140, 581-589.

  • 16. Gonzalez-Juarrero M., Mebus C.A., Pan R., Revilla Y., Alonso J.M., Lunney J.K.: Swine leukocyte antigen and macrophage marker expression on both African swine fever virusinfected and non-infected primary porcine macrophage cultures. Vet Immunol Immunopathol 1992, 32, 243-259.

  • 17. Gordon S., Plüddemann A., Martinez Estrada F.: Macrophage heterogeneity in tissues: phenotypic diversity and functions. Immunol Rev 2014, 262, 36-55.

  • 18. Granja A.G., Sanchez E.G., Sabina P., Fresno M., Revilla Y.: African swine fever virus blocks the host cell antiviral inflammatory response through a direct inhibition of PKC-theta-mediated p300 transactivation. J Virol 2009, 83, 969-980.

  • 19. Haak-Frendscho M., Wynn TA., Czuprynski C.J., Paulnock D.: Transforming growth factor-beta 1 inhibits activation of macrophage cell line RAW 264.7 for cell killing. Clin Exp Immunol 1990, 82, 404-410.

  • 20. Haverson K., Bailey M., Higgins V.R., Bland P.W., Stokes C.R.: Characterization of monoclonal antibodies specific for monocytes, macrophages and granulocytes from porcine peripheral blood and mucosal tissues. J Immunol Methods 1994, 170, 233-245.

  • 21. Kreutz M., Andreesen R., Krause S.W., Szabo A., Ritz E., Reichel H.: 1,25-dihydroxyvitamin D3 production and vitamin D3 receptor expression are developmentally regulated during differentiation of human monocytes into macrophages. Blood 1993, 82, 1300-1307.

  • 22. Kusano Y., Yoshitomi Y., Munesue S., Okayama M., Oguri K.: Cooperation of syndecan-2 and syndecan-4 among cell surface heparan sulfate proteoglycans in the actin cytoskeletal organization of Lewis lung carcinoma cells. J Biochem 2004, 135, 129-137.

  • 23. Leitão A., Cartaxeiro C., Coelho R., Cruz B., Parkhouse R.M.E., Portugal F.C., Vigário J.D., Martins C.L.V.: The non-hemadsorbing African swine fever virus isolate ASFV/NH/P68 provides a model for defining the protective anti-virus immune response. J Gen Virol 2001, 82, 513-523.

  • 24. McCullough K.C., Schaffner R., Natale V., Kim Y.B., Summerfield A.: Phenotype of porcine monocytic cells: modulation of surface molecule expression upon monocyte differentiation into macrophages. Vet Immunol Immunopathol 1997, 58, 265-275.

  • 25. Mendoza C., Videgain S.P., Alonso F.: Inhibition of natural killer activity in porcine mononuclear cells by African swine fever virus. Res Vet Sci 1991, 51, 317-321.

  • 26. Powell P.P., Dixon L.K., Parkhouse R.M.: An IkappaB homolog encoded by African swine fever virus provides a novel mechanism for downregulation of proinflammatory cytokine responses in host macrophages. J Virol 1996, 70, 8527-8533.

  • 27. Rodriguez A., Meyerson H., Anderson J.M.: Quantitative in vivo cytokine analysis at synthetic biomaterial implant sites. J Biomed Mater Res A 2009, 89, 152-159.

  • 28. Salguero F.J., Sánchez-Cordón P.J., Núñez A., Fernández de Marco M., Gómez-Villamandos J.C.: Proinflammatory cytokines induce lymphocyte apoptosis in acute African swine fever infection. J Comp Pathol 2005, 132, 289-302.

  • 29. Sánchez E.G., Quintas A., Pérez-Núñez D., Nogal M., Barroso S., Carrascosa Á.L., Revilla Y.: African swine fever virus uses macropinocytosis to enter host cells. PLoS Pathog 2012, 8, e1002754.

  • 30. Suzuki H., Katayama N., Ikuta Y., Mukai K., Fujieda A., Mitani H., Araki H., Miyashita H., Hoshino N., Nishikawa H., Nishii K., Minami N., Shiku H.: Activities of granulocyte-macrophage colony-stimulating factor and interleukin-3 on monocytes. Am J Hematol 2004, 75, 179-189.

  • 31. Vallée I., Tait S.W., Powell P.P.: African swine fever virus infection of porcine aortic endothelial cells leads to inhibition of inflammatory responses, activation of the thrombotic state, and apoptosis. J Virol 2001, 75, 10372-10382.

  • 32. Whittall J.T., Parkhouse R.M.: Changes in swine macrophage phenotype after infection with African swine fever virus: cytokine production and responsiveness to interferon-gamma and lipopolysaccharide. Immunology 1997, 91, 444-449.

  • 33. Wierda W.G., Johnson B.D., Dato M.E., Kim Y.B.: Induction of porcine granulocyte-mediated tumor cytotoxicity by two distinct monoclonal antibodies against lytic trigger molecules (PNK-E/G7). J Immunol 1993, 151, 7117-7127.

  • 34. Zhang F., Hopwood P., Abrams C.C., Downing A., Murray F., Talbot R., Archibald A., Lowden S., Dixon L.K.: Macrophage transcriptional responses following in vitro infection with a highly virulent African swine fever virus isolate. J Virol 2006, 80, 10514-10521.


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